Phase 1/1b/2 Study of Oral PMD-026 in Patients with Metastatic Breast Cancer

Open to people ages 18 years and up

, Combination with fulvestrant (Part 3):

• Available archival or FFPE
• RSK2 positive (≥75% nuclear staining with ≥2+ in staining intensity) as assessed by central lab from available archival or fresh tumor tissue (FFPE).
• Histologically or cytologically diagnosed HR+, HER2- defined as both
  • >1% expression of ER and/or PgR receptor
  • ≤ 1+ by IHC for HER2, or FISH negative. If 2+ by IHC for HER2 combined with FISH negative
• Diagnosis of adenocarcinoma of the breast with evidence of either locally advanced disease not amendable to resection or radiation with curative intent or metastatic disease not amendable to curative therapy
• Must be appropriate candidates for endocrine therapy
• Previously received at least 1 line of endocrine therapy for MBC or had recurrence while on adjuvant endocrine therapy for locally advanced breast cancer
• Discontinued endocrine therapy at least 15 days prior to first dose of PMD-026
• At least 1 measurable target lesion as defined by RECIST v1.1
• Progression on or after treatment with a CDK4/6 inhibitor in combination with endocrine therapy inhibitor in the locally advanced or metastatic setting
• Has not received fulvestrant in the locally advanced or metastatic setting. Note: If prior to study entry, a patient initiates fulvestrant in combination with targeted therapy and becomes intolerant of the targeted therapy before progression, that patient may enroll if PMD-026 is initiated within 48 days of start of fulvestrant and no missed doses of fulvestrant occurred.
• Not eligible for an AKT or PI3K inhibitor
• Adequate hematologic, hepatic, and renal function as assessed by laboratory parameters
• Toxicity related to prior therapy resolved to at least Grade 1 (alopecia excepted) or to at least Grade 2 with prior approval of the Medical Monitor

, Combination with fulvestrant (Part 3):

• ≤14 days from prior chemotherapy, biological or investigational therapy
• Prior fulvestrant in the locally advanced or metastatic setting
• Presence of visceral crisis or uncontrolled visceral disease for which chemotherapy would be indicated
• Central nervous system metastases, unless appropriately treated and neurologically stable
• History of leptomeningeal metastases
• Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
• Known hepatitis B or hepatitis C infection
• Known HIV-positive with CD4+ cell counts <350 cells/μL
• Known HIV-positive with a history of an AIDS-defining opportunistic infection
• History of clinically significant cardiovascular abnormalities, including QTcF interval >460 msec (using Fridericia's formula)